Interaction between HLA-B60 and HLA-B27 as a Better Predictor of Ankylosing Spondylitis in a Taiwanese Population

James Cheng-Chung Wei; Henry Wong Sung-Ching; Yu-Wen Hsu; Ya-Feng Wen; Wen-Chang Wang; Ruey-Hong Wong; Hsing-Fang Lu; Floris A van Gaalen; Wei-Chiao Chang

doi:10.1371/journal.pone.0137189

Interaction between HLA-B60 and HLA-B27 as a Better Predictor of Ankylosing Spondylitis in a Taiwanese Population

PLoS One. 2015 Oct 15;10(10):e0137189. doi: 10.1371/journal.pone.0137189. eCollection 2015.

Authors

James Cheng-Chung Wei¹, Henry Wong Sung-Ching², Yu-Wen Hsu³, Ya-Feng Wen⁴, Wen-Chang Wang⁵, Ruey-Hong Wong⁶, Hsing-Fang Lu⁷, Floris A van Gaalen⁸, Wei-Chiao Chang⁹

Affiliations

¹ Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Institute of Intergrative Medicine, China Medical University, Taichung, Taiwan.
² Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
³ Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Tiawan.
⁴ Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
⁵ Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; The Ph.D. Program for Translational Medicine, Taipei Medical University, Taipei, Taiwan.
⁶ Department of Public Health, Chung Shan Medical University, Taichung, Taiwan; Department of Occupational Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁷ Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Pharmacy, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
⁸ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

Objective: Ankylosing spondylitis (AS) is a form of chronic inflammatory spondyloarthritis (SpA) that causes pain and stiffness in spines or joints. Human leukocyte antigen B27 (HLA-B27) and B60 (HLA-B60) have been reported as major genetic risk factors of AS. In addition, rs13202464, located on major histocompatibility complex (MHC) region, showed high sensitivity (98.7%) and specificity (98.0%) for HLA-B27.

Design: The aim of our study is to test whether the interaction between HLA-B60 and HLA-B27 (rs13202464) can serve as a better predictor of AS. We have genotyped HLA-B60 and rs13202464 among 471 patients with AS and 557 healthy subjects. Combined risk factors were investigated to test the biological interaction.

Results: Our results indicated that the relative risk (RR) for HLA-B27+/HLA-B60- was 152 (95% CI 91 to 255) and it increased to 201 (95% CI 85 to 475) in HLA-B27+/HLA-B60+ patients (with HLA-B27-/HLA-B60- as reference). Combinational analysis of two risk factors (HLA-B27+/HLA-B60+) showed a relative excess risk due to interaction (RERI) of 46.79 (95% CI: -117.58 to 211.16), attributable proportion (AP) of 0.23 (95% CI: -0.41 to 0.88) and a synergy index (S) of 1.31 (95% CI: 0.56 to 3.04).

Conclusion: In conclusion, genetic interaction analysis revealed that the interaction between HLA-B60 and HLA-B27 is a better marker for the risk of AS susceptibility in a Taiwanese population.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Asian People / genetics*
Case-Control Studies
Epistasis, Genetic*
Female
Genetic Predisposition to Disease*
HLA-B Antigens / genetics*
HLA-B27 Antigen / genetics*
Humans
Male
Middle Aged
Spondylitis, Ankylosing / genetics*
Taiwan
Young Adult

Substances

HLA-B Antigens
HLA-B27 Antigen
HLA-B60 antigen

Grants and funding

Supported by a research grant from Chung Shan Medical University Hospital, No CSH-2009-C-006 to Dr. Wei JC and a research grant from National Science Council, Taiwan, ROC (MOST 104-2320-B-038-016; NSC101-2628-B038-001-MY2;TMU101-AE4-B14) to Dr. Chang WC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.